Immunoglobulins (Ig) or antibodies are glycoprotein molecules that are produced by a type of white blood cells called B cells. These molecules are used by a host's immune system to identify and neutralize foreign objects, such as bacteria, viruses, and other pathogens. In placental mammals, there are five types of immunoglobulins, viz., IgA, IgD, IgE, IgG, and IgM that differ in their biological properties, functional locations and ability to respond to specific antigens.
Naïve B cells that have never been exposed to an antigen express only IgM. Mature B cells express both IgM and IgD; the co-expression of both IgM and IgD renders the B cells ready to respond to an antigen. When a cell bound antibody engages with an antigen, the B cells divide and differentiate into an antibody-producing cell called plasma cell or activated B cell. Certain activated B cells are capable of producing all five types of immunoglobulins, including IgE, IgA and IgG that have defined roles in the immune system.
Amongst the different types of immunoglobulins, IgG is the most predominant immunoglobulin in serum (about 75%) and is also the major immunoglobulin in extravascular spaces. IgG provides the majority of antibody-based immunity against invading pathogens. IgG is also the only class of immunoglobulin capable of crossing the placenta to give passive immunity to fetus.
The measurement of levels of individual types of immunoglobulins present in serum of a patient provides an antibody profile of the patient that can be used for diagnostic purposes. A deviation from a normally expected immunoglobulin level serves as an indication of a particular immunoglobulin disorder. For example, IgG levels increase in most infections such as chronic granulomatous infections; hyperimmunizations; liver diseases; severe malnutrition; dysprotenemia; hypersensitivity granulomas; dermatologic disorders; IgG myeloma; rheumatoid arthritis etc. On the other hand, IgG levels decrease in conditions such as agammaglobulimia; lymphoid aplasia; selective IgG and IgA deficiencies; IgA myeloma; Bence Jones proteinemia, chronic lymphoblastic leukemia etc.
Several tests are commonly used for the measurement of immunoglobulin concentrations in general and IgG in particular. For example, radial immunodiffusion assay (RID) is considered the gold standard test for quantitative measurement of IgG. In addition, enzyme-linked immunosorbent assays (ELISA) have been used as screening tests that measure the IgG concentration with a species-specific anti-IgG antibody. Other tests, such as the glutaraldehyde coagulation test, calorimetric assay, zinc sulfate turbidity measurements, tubimetric immunoassay, lateral flow immunoassay etc., can also be used, but these are non-specific since they detect other serum proteins in addition to immunoglobulins. These tests are primarily screening tests and hence have good sensitivity (comparable with RID), but have limited specificity.
While the RID assay provides quantitative IgG data, it requires 18-24 h to obtain results, requires more technical skill that the alternatives, is not amenable to automation, and is often more expensive than the alternatives.
It is, therefore, desirable to provide a rapid test for diagnosis of immunoglobulin disorders that is both highly sensitive and highly specific.